title: 2-(2-Hydrazinyl)thiazole derivatives: design, synthesis and in vitro antimycobacterial studies.
abstract: In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their inhibitory potential against Mtb, H₃₇Rv, by in vitro assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and ethyl-2-[(E)-2-[(2-hydroxyphenyl)methylidene]hydrazin-1-yl]-4-methyl-1,3-thiazole-5-carboxylate, 2i showed noticeable inhibitory activity against Mtb, H37Rv with minimum inhibitory concentration (MIC) of 12.5 μM and 25 μM respectively. An attempt has been made to understand the mechanism of action by binding interactions of these molecules with β-ketoacyl-ACP synthase protein through docking studies. The inhibition constants for compounds 4d and 2i were found to be 1.46 μM and 0.177 μM respectively.
authors.affiliation: Department of Chemistry, Pondicherry University, Puducherry 605 014, India.
authors.forename: Parameshwar
authors.initials: P
authors.lastname: Makam
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Kankanala
authors.forename: Amresh
authors.initials: A
authors.lastname: Prakash
authors.forename: Tharanikkarasu
authors.initials: T
authors.lastname: Kannan
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; D013844:Thiazoles
keywords: AJLNXGLZYKBIHV-OVCLIPMQSA-N; ATCLBIWNPGMWSG-OVCLIPMQSA-N; AWQCONSMQKVQBL-GIJQJNRQSA-N; BCYRWBFBAGDLIB-OVCLIPMQSA-N; BLPWXDDAGXSZNF-OVCLIPMQSA-N; DDNNZKRMRHKNQS-LICLKQGHSA-N; DYBJAZJOMGWGMU-LZYBPNLTSA-N; GLONTBYWQCQJPI-CXUHLZMHSA-N; H(37)Rv; HSJDULXAYHDAAN-LICLKQGHSA-N; HXVSXELBPPIAPZ-RQZCQDPDSA-N; IOEMKPCIYUVUTA-LICLKQGHSA-N; IQWRIXJIVQEGRB-FRKPEAEDSA-N; IULVWCSWFBMHJK-CAOOACKPSA-N; KOQVGOKQWDKPML-LICLKQGHSA-N; LZGGZLIPZOLCIR-LZYBPNLTSA-N; Lipinski rule; Mycobacterium tuberculosis; NDMLDJHDLLJDGO-VCHYOVAHSA-N; NUOSUXUGASOFFG-CAOOACKPSA-N; NZQFXGZUKPADMY-OVCLIPMQSA-N; OEPJZLZXEYSGNE-RQZCQDPDSA-N; OXBYVSSRYGMHPL-RQZCQDPDSA-N; PCHGOUYNSVFNRU-GIJQJNRQSA-N; QBCSKDDXCWSUIG-OQLLNIDSSA-N; QUTYCERHMJSUCI-GIJQJNRQSA-N; REWRLGKLBXIIHM-RQZCQDPDSA-N; RWKFMSDAGJMQGY-REZTVBANSA-N; SHVRDDAHKAYCDP-CXUHLZMHSA-N; TXEVAFMZVNPKTA-GIJQJNRQSA-N; Thiazole; Tuberculosis; UQRBVVWLXGAPDW-LZYBPNLTSA-N; VIVKMRRNLSXCDL-GIDUJCDVSA-N; VXHXOFMJZUBWBO-NTUHNPAUSA-N; WNVXUJRPBZSDLD-RQZCQDPDSA-N; YYDXDTMFUWSCQH-OVCLIPMQSA-N; ZEDHGYXLWKHHBR-OMCISZLKSA-N; ZKNJICDVJPXFAO-LZYBPNLTSA-N; ZXQUYAHQNLDHRY-LZYBPNLTSA-N; β-Ketoacyl-ACP synthase